Catalysts are an important component for many chemical reactions as they typically increase the rate of the reaction. They may also inhibit the formation of competing products as there is less time for significant product formation by competing reactions. Beyond improving reaction rate and enhancing product yield, catalysts may also provide an enantioselective mechanism for obtaining an optically active product. Often an enantioselective catalyst is itself chiral and optically active. There is a need for the development of enantioselective catalysts to catalyze reactions resulting in optically active products. Many naturally occurring and biologically active molecules are optically active and many reaction mechanisms, especially biological reactions, only function with compounds having a specific enantiomeric configuration.
Chiral catalysts have been used in a wide variety of reactions. One such reaction is the enantioselective alkylation of an aldehyde with an organozinc reagent to produce an optically active secondary alcohol. These optically active alcohols are components of many naturally occurring and biologically active compounds, as well as materials such as liquid crystals. Optically active alcohols are also important as synthetic intermediates of various functionalities such as halide, amine, ester, ether, etc.
Organozinc compounds have proven useful in the formation of optically active secondary alcohols. However, the simple addition of an organozinc compound to an aldehyde does not typically produce an optically active alcohol since the starting aldehyde and organozinc compound are often not optically active. In addition, the reaction of an organozinc compound, especially a dialkylzinc compound, with an aldehyde is often very slow and results in side reactions such as reduction. Chiral catalysts are useful in this reaction to increase the reaction rate, reduce the amount of side reaction products, and provide chiral centers that increase the enantioselectivity of the reaction.
There have been many chiral catalysts developed for use in this reaction. See reviews by Soai, et al., Chem. Rev., 92, 833 (1992) and Noyori, et al., Angew. Chem. Int. Ed. Engl., 30, 49 (1991). However, many of these catalysts are useful only in reactions with a specific type of substrate (e.g., aliphatic aldehydes or aromatic aldehydes). There is a need for the development of additional catalysts and, in particular, catalysts which can be used with a broad spectrum of substrates.